The goal of the proposed research project is to investigate the effects of estrogen on central monoamine neurons. Estrogen?s role in the brain is still largely unknown, although the ability of estrogen to modulate central monoamine function has been recognized. The clinical relevance of this observation lies in the fact that women are twice as likely to suffer from depression than men, and depression seems to be associated with a perturbation of central monoamine function. In addition, drugs that target monoaminergic neurotransmission, specificaIIy norepinephrine (NE), have proven successful in the treatment of depression. There are two estrogen receptors, ER alpha and ER beta, each with unique transcriptional properties and tissue distribution, suggesting that each receptor has a unique biological role. We have shown that ER beta, but not ER alpha, is expressed in cath.a cells, an immortalized cell line derived from central noradrenergic neurons. NE neurons are the only monoamine neurons in the rat that express ER, and several studies show that estrogen is inhibitory to the production of several proteins relevant for NE synthesis. I propose to study the expression, pharmacology, and functions of ER beta in this cell culture system, and compliment these studies using intact NE neurons of the locus coeruleus from which these cells are derived. Understanding the transcriptional properties of ER beta in central monoamine neurons will increase the understanding of the role of estrogen in affective disorders, and will provide broadly applicable information to other fields including endocrinology and breast cancer biology.